The dynamicity of acute ozone-induced systemic leukocyte trafficking and adrenal-derived stress hormones.

• Ozone within 2-h depletes circulating immune cells prior to lung inflammation. • Increases in epinephrine and corticosterone precede immune cell depletion in blood. • Small changes in circulating cytokines occur after increases in blood stress hormones. • Rise in classical monocytes at 30 min and then a decline suggests lung extravasation. • Ozone-induced depletion of B and T lymphocytes at 2-h suggests margination to lung. Ozone exposure induces neuroendocrine stress response, which causes lymphopenia. It was hypothesized that ozone-induced increases in stress hormones will temporally follow changes in circulating granulocytes, monocytes- and lymphocyte subpopulations. The goal of this study was to chronicle the changes in circulating stress hormones, cytokines, and leukocyte trafficking during 4 h exposure to ozone. Male Wistar Kyoto rats were exposed to air or ozone (0.4 or 0.8 ppm) for 0.5, 1, 2, or 4 h. After each time point, circulating stress hormones, cytokines, and lung gene expression were assessed along with live and apoptotic granulocytes, monocytes (classical and non-classical), and lymphocytes (B, T h , and T c) in blood, thymus, and spleen using flow cytometry. Circulating stress hormones began to increase at 1 h of ozone exposure. Lung expression of inflammatory cytokines (Cxcl2 , Il6 , and Hmox1) and glucocorticoid-responsive genes (Nr3c1 , Fkbp5 and Tsc22d3) increased in both a time- and ozone concentration-dependent manner. Circulating granulocytes increased at 0.5 h of ozone exposure but tended to decrease at 2 and 4 h, suggesting a rapid egress and then margination to the lung. Classical monocytes decreased over 4 h of exposure periods (∼80 % at 0.8 ppm). B and T c lymphocytes significantly decreased after ozone exposure at 2 and 4 h. Despite dynamic shifts in circulating immune cell populations, few differences were measured in serum cytokines. Ozone neither increased apoptotic cells nor altered thymus and spleen lymphocytes. The data show that ozone-induced increases in adrenal-derived stress hormones precede the dynamic migration of circulating immune cells, likely to the lung to mediate inflammation. [ABSTRACT FROM AUTHOR]